rs10520481

Variant names:

• chr19-52209128-C-T
• rs10520481
• NM_014225.6:c.271-2132C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014225.6(PPP2R1A):​c.271-2132C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 152,250 control chromosomes in the GnomAD database, including 547 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.081 (547 hom., cov: 32)
• Consequence: PPP2R1A NM_014225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711
• Publications: 7 publications found

Genes affected

PPP2R1A (HGNC:9302): (protein phosphatase 2 scaffold subunit Aalpha) This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes an alpha isoform of the constant regulatory subunit A. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

PPP2R1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Houge-Janssens syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R1A	NM_014225.6	c.271-2132C>T		intron_variant	Intron 3 of 14	ENST00000322088.11	NP_055040.2
PPP2R1A	NM_001363656.2	c.-267-2132C>T		intron_variant	Intron 3 of 14		NP_001350585.1
PPP2R1A	NR_033500.2	n.215-2132C>T		intron_variant	Intron 2 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R1A	ENST00000322088.11	c.271-2132C>T		intron_variant	Intron 3 of 14	1	NM_014225.6	ENSP00000324804.6

Frequencies

GnomAD3 genomes AF: 0.0810 AC: 12330 AN: 152132 Hom.: 546 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0752

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0540

Gnomad FIN AF: 0.0645

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.0860

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0811 AC: 12346 AN: 152250 Hom.: 547 Cov.: 32 AF XY: 0.0792 AC XY: 5897 AN XY: 74446

African (AFR) AF: 0.101 AC: 4203 AN: 41536

American (AMR) AF: 0.0754 AC: 1153 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 338 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5186

South Asian (SAS) AF: 0.0546 AC: 264 AN: 4832

European-Finnish (FIN) AF: 0.0645 AC: 685 AN: 10612

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0794 AC: 5398 AN: 68006

Other (OTH) AF: 0.0851 AC: 180 AN: 2114

Alfa AF: 0.0805 Hom.: 863

Bravo AF: 0.0831

Asia WGS AF: 0.0290 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10520481; hg19: chr19-52712381;